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Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index
<span title="2011-05-04">2011</span>
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Genetic polymorphisms in the gene encoding the b-adrenergic receptors (b-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype-phenotype analysis to investigate the association between b-AR gene polymorphisms and heart rate dynamics. Methods: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6610.8 years, range 19 to 63 years) were recruited
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<a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pone.0019232">doi:10.1371/journal.pone.0019232</a>
<a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/21573230">pmid:21573230</a>
<a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3087751/">pmcid:PMC3087751</a>
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... genotyped for three common b-AR polymorphisms: b 1 -AR Ser49Gly, b 2 -AR Arg16Gly and b 2 -AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. Results: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of b 2 -AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. Conclusions: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with b-AR polymorphisms. Our results provide evidence that b 2 -AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.
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